Work is in progress to understand the regulatory mechanisms of HIV replication using in vitro culture systems and patient specimens. Virologic analysis of a group of non progressors indicates that in general the viral load (plasma viral RNA) is lower in non progressors than in persons who progress rapidly. Also, virus can be isolated more frequently from progressors than non progressors. Our laboratory has isolated virus from a few non progressors and progressors and is currently performing genetic analysis of the viral regulatory genes and the LTR and env sequences by nucleotide sequencing. The tropism of these isolates is being studied in a variety of cell lines. Future studies are aimed at understanding the role of certain chemokines and cytokines in the establishment of the non progressive phenotype. Studies are also underway to evaluate the replication of HIV-1 Group O viruses in in vitro cell systems. Preliminary results indicate that these viruses grow well in PBMCs but not in a variety of cell types of T cell and monocytic origin. We are further pursuing these investigations by evaluating their infectivity in additional cell lines of T cell and monocyte origin and in purified cultures for primary T cell and monocytic origin. The goal of this work is to compare the replication and infectivity of group O viruses with group M viruses with regard to tropism and cellular pathways involved in viral pathogenesis.